HUMAN IMMUNE DISORDERS

The immune system can be viewed as an internal machine with the different parts working together to fight off threats from invading pathogens. We know that this complex array of interactions is usually very effective, as although we are likely to be faced with antigenic insults on a daily basis, we are rarely fraught by infection.

However, on occasion, and some people more frequently than others, we do succumb to infection. This can be compounded by factors such as stress, lack of sleep or poor diet, but the underlying cause is that our immune system has failed at doing its job. Whenever we are faced with a pathogen our immune system has to recognise this pathogen as a foreign body, what type it is and decide what is the best way of dealing with it. It is imperative that we dissect and understand the different mechanisms of the immune response such that we can identify appropriate therapies for disease treatment and prevention such as with vaccines.

We have chosen to study the workings of the immune system by investigating primary human imunodeficiencies. These are patients with mutations in a single gene, which renders them vulnerable to infection. Depending on the gene, the affected patient can present with quite severe disease. An example of this would be the “boy in the bubble” who had severe combined immunodeficiency (SCID) due to a mutation in IL-2RG or the common gamma chain. However, surprisingly, in some instances patients with these gene mutations do not present with overwhelming immunodeficiency, but rather they display susceptibility to a very narrow spectrum of infections.

For example patients with mutations in the gene encoding a protein termed SAP are only susceptible to infection with Epstein Barr virus (EBV), which causes glandular fever. In fact, by studying patients with defects in SAP expression, we have gained invaluable insight into how the immune system deals with EBV infections. Through investigating patients with immunodeficiencies we hope to establish the type of responses required for the elimination of different pathogens and identify novel therapies for the treatment of immunodeficiencies and other diseases whereby the immune system is compromised.